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Pyroglutamate Aβ cascade as drug target in Alzheimer's disease
Bayer TA.. Molecular psychiatry, 2021-12-08
Topic: Amyloid, tau and blood-test diagnosis
One of the central aims in Alzheimer's disease (AD) research is the identification of clinically relevant drug targets. A plethora of potential molecular targets work very well in preclinical model systems both in vitro and in vivo in AD mouse models. However, the lack of translation into clinical settings in the AD field is a challenging endeavor. Although it is long known that N-terminally truncated and pyroglutamate-modified Abeta (Aβ pE3 ) peptides are abundantly present in the brain of AD patients, form stable and soluble low-molecular weight oligomers, and induce neurodegeneration in AD mouse models, their potential as drug target has not been generally accepted in the past. This situation has dramatically changed with the report that passive immunization with donanemab, an Aβ pE3 -specific antibody, cleared aymloid plaques and stabilized cognitive deficits in a group of patients with mild AD in a phase II trial. This review summarizes the current knowledge on the molecular mechanisms of generation of Aβ pE , its biochemical properties, and the intervention points as a drug target in AD.
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APA 7th
Bayer, T. A. (2022). Pyroglutamate Aβ cascade as drug target in Alzheimer's disease. Molecular psychiatry. https://doi.org/10.1038/s41380-021-01409-2
Vancouver
Bayer TA. Pyroglutamate Aβ cascade as drug target in Alzheimer's disease. Molecular psychiatry. 2022. doi:10.1038/s41380-021-01409-2. PMID: 34880449.
BibTeX
@article{bayer2022-34880449,
author = {Bayer, T. A.},
title = {{Pyroglutamate Aβ cascade as drug target in Alzheimer's disease}},
journal = {Molecular psychiatry},
year = {2022},
doi = {10.1038/s41380-021-01409-2},
pmid = {34880449},
url = {https://doi.org/10.1038/s41380-021-01409-2}
}
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Key findings
- A plethora of potential molecular targets work very well in preclinical model systems both in vitro and in vivo in AD mouse models.
- However, the lack of translation into clinical settings in the AD field is a challenging endeavor.
- Although it is long known that N-terminally truncated and pyroglutamate-modified Abeta (Aβ pE3 ) peptides are abundantly present in the brain of AD patients, form stable and soluble low-molecular weight oligomers, and induce neurodegeneration in AD mouse models, their potential as drug target has not been generally accepted in the past.
- This situation has dramatically changed with the report that passive immunization with donanemab, an Aβ pE3 -specific antibody, cleared aymloid plaques and stabilized cognitive deficits in a group of patients with mild AD in a phase II trial.
- This review summarizes the current knowledge on the molecular mechanisms of generation of Aβ pE , its biochemical properties, and the intervention points as a drug target in AD.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34880449) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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